3. Receptor enzymes Page: 429 Difficulty: 2 Ans: B Which of the following statements concerning receptor enzymes is correct? A) B) C) D) E) They are not usually membrane-associated proteins. They contain an enzyme activity that acts upon a cytosolic substrate. They contain an enzyme activity that acts upon the extracellular ligand. They have a ligand-binding site on the cytosolic side of the membrane. They have an active site on the extracellular side of the membrane.

4. G protein-coupled receptors and second messengers Page: 441 Difficulty: 2 Ans: C Which of the following does not involve cyclic AMP?

A) B) C) D) E)

Regulation of glycogen synthesis and breakdown Regulation of glycolysis Signaling by acetylcholine Signaling by epinephrine Signaling by glucagon

Short Answer Questions

8. Receptor enzymes Page: 433 Difficulty: 3 Explain how the cytokine erythropoetin activates transcription of specific genes essential in blood maturation. Ans: Binding of erythropoetin to its plasma membrane receptor causes the receptor to dimerize. The soluble cytoplasmic protein kinase JAK can now bind to receptor, become activated, and phosphorylate three tyrosine residues on the receptor, some of which in turn are bound by the STAT5 transcription factor, positioning it for phosphorylation by JAK. The phosphorylated STAT5 then dimerizes, facilitating its transport into the nucleus, where it activates transcription of specific genes essential in blood maturation.

9. G Protein-coupled receptors and second messengers

Chapter 12 Biosignaling

135

Pages: 436-443 Difficulty: 3 GTP-binding proteins play critical roles in many signal transductions. Describe two cases in which such proteins act, and compare the role of the G proteins in each case. Ans: GTP-binding proteins are self-inactivating switches; when a hormonal or other signal activates the G protein, GTP replaces bound GDP, changing the activity of the G protein. These active G proteins then act on the next element in the signaling cascade. In the case of the -adrenergic receptor, Gs activates adenylate cyclase; in the IP3 pathways, Gp activates the phospholipase that generates the second messengers diacylglycerol and IP3. (See Figs. 12-12, p. 436, and 12-19, p. 443.)

10. G Protein-coupled receptors and second messengers Page: 439 Difficulty: 3 Describe the sequence of biochemical events between the release of epinephrine into the bloodstream and the activation of the enzyme glycogen phosphorylase. Ans: Epinephrine binds to its specific receptor on the cell surface. The occupied receptor causes GTP for GDP exchange on a GTP-binding protein (Gs); Gs then activates adenylate cyclase of the plasma membrane, which catalyzes production of 3',5'-cyclic AMP (cAMP). The cAMP-dependent protein kinase (protein kinase A) is activated by the resulting rise in cAMP, and it phosphorylates the enzyme phosphorylase kinase, activating it. Active phosphorylase kinase phosphorylates glycogen phosphorylase, activating it and stimulating glycogen breakdown. (See Fig. 12-16, p. 439.)

11. Regulation of cell cycle by protein kinases Pages: 467-470 Difficulty: 2 What are cyclins? What is their role in the regulation of the cell cycle? Ans: Cyclins are regulatory subunits of protein kinases. The presence of the cyclin subunits is essential for activation of the protein kinase activity. The levels of cyclins fluctuate during the cell cycle and in response to cellular and extracellular signals. These changes result in changes in the activities of the cyclin-dependent protein kinases that in turn regulate and control the cell cycle.

12. Oncogenes, tumor suppressor genes and programmed cell death Page: 472 Difficulty: 3 The product of the erbB oncogene closely resembles the cellular receptor for epidermal growth factor (EGF). How do the two proteins differ, and how does this difference account for the oncogenic action of the ErbB protein? Ans: The EGF receptor is a transmembrane receptor with tyrosine kinase activity that is stimulated by EGF bound to the extracellular domain of the protein. The ErbB protein is a truncated version of the EGF receptor, in which the tyrosine kinase activity is always active, even in the absence of EGF, because the protein lacks the EGF-binding domain. The kinase activity gives the cell the signal for continuous growth and cell division, producing the unregulated growth that characterizes tumors. (See Fig. 12-48, p. 472.)